JAK/STAT – Emerging Players in Metabolism

Dodington, David W.; Desai, Harsh R.; Woo, Minna

doi:10.1016/j.tem.2017.11.001

Cited by 214 publications

(180 citation statements)

References 78 publications

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“…The SOCS3 is well known as a feedback inhibitor of the JAK/STAT3 signaling pathway [22]. JAK/STAT signaling pathway can activate type I IFN [24]. The expression of antiviral factors OAS2 and MX1 depends on type I IFN regulation [20,21].…”

Section: Discussionmentioning

confidence: 99%

Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

Gao

Huang

Liu

et al. 2020

BioMed Research International

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Enterovirus 71 (EV71) is the causative pathogen of hand, foot, and mouth disease (HFMD). However, no effective antiviral therapy is currently available. Some viruses could escape the host’s innate immunity by upregulating suppressor of cytokine signaling (SOCS) proteins. Until now, whether EV71 evades the host immune system by regulating the expression of SOCS proteins remains unknown. In this study, we found that EV71 infection promoted SOCS expression at both mRNA and protein levels in vitro and in vivo. Consistently, the infectivity of EV71 was decreased significantly in the SOCS3 or SOCS1 knockdown cells, suggesting that SOCS1 and especially SOCS3 are crucial for EV71 infection. Further investigation showed that SOCS3 promoted virus infection by inhibiting interferon-induced STAT3 phosphorylation. SOCS1 and SOCS3 mRNA expressions were independent on virus-induced type I interferon expression but were blocked by the inhibitor of NF-κB. Therefore, EV71 infection stimulates the expression of SOCS proteins in an interferon-independent way and negatively regulates the JAK/STAT signaling pathway, thus escaping host immunity. All these results may add new information to the mechanism of EV71 in fighting against type I interferon responses.

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Section: Discussionmentioning

confidence: 99%

Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

Gao

Huang

Liu

et al. 2020

BioMed Research International

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“…This score was used to reflect a metabolic health profile, with a higher score indicating a poorer profile. This scoring system has been previously validated in the European multicenter Identification Using previous knowledge from the Kyoto Encyclopedia of Genes and Genomes database, we grouped proteins into 5 pathways that are considered to play key roles in inflammation and cardiometabolic health: the Janus kinase signal transducer and activator of transcription proteins signaling pathway, 29 the adipocytokine signaling pathway, 30 the cholesterol metabolism pathway, 31 the nuclear factor-kappa B pathway, 32 and the chemokine signaling pathway. 33…”

Section: Adiposity Lipid Levels and Blood Pressurementioning

confidence: 99%

Association of Fish Consumption and Mercury Exposure During Pregnancy With Metabolic Health and Inflammatory Biomarkers in Children

et al. 2020

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IMPORTANCE The balance of mercury risk and nutritional benefit from fish intake during pregnancy for the metabolic health of offspring to date is unknown.OBJECTIVE To assess the associations of fish intake and mercury exposure during pregnancy with metabolic syndrome in children and alterations in biomarkers of inflammation in children. DESIGN, SETTING, AND PARTICIPANTSThis population-based prospective birth cohort study used data from studies performed in 5 European countries (France, Greece, Norway, Spain, and the UK) between April 1, 2003, and February 26, 2016, as part of the Human Early Life Exposome (HELIX) project. Mothers and their singleton offspring were followed up until the children were aged 6 to 12 years. Data were analyzed between March 1 and August 2, 2019.EXPOSURES Maternal fish intake during pregnancy (measured in times per week) was assessed using validated food frequency questionnaires, and maternal mercury concentration (measured in micrograms per liter) was assessed using maternal whole blood and cord blood samples. MAIN OUTCOMES AND MEASURESAn aggregate metabolic syndrome score for children was calculated using the z scores of waist circumference, systolic and diastolic blood pressures, and levels of triglyceride, high-density lipoprotein cholesterol, and insulin. A higher metabolic syndrome score (score range, −4.9 to 7.5) indicated a poorer metabolic profile. Three protein panels were used to measure several cytokines and adipokines in the plasma of children. RESULTSThe study included 805 mothers and their singleton children. Among mothers, the mean (SD) age at cohort inclusion or delivery of their infant was 31.3 (4.6) years. A total of 400 women (49.7%) had a high educational level, and 432 women (53.7%) were multiparous. Among children, the mean (SD) age was 8.4 (1.5) years (age range, 6-12 years). A total of 453 children (56.3%) were boys, and 734 children (91.2%) were of white race/ethnicity. Fish intake consistent with health recommendations (1 to 3 times per week) during pregnancy was associated with a 1-U decrease in metabolic syndrome score in children (β = −0.96; 95% CI, −1.49 to −0.42) compared with low fish consumption (<1 time per week) after adjusting for maternal mercury levels and other covariates. No further benefit was observed with fish intake of more than 3 times per week. A higher maternal mercury concentration was independently associated with an increase in the metabolic syndrome score of their offspring (β per 2-fold increase in mercury concentration = 0.18; 95% CI, 0.01-0.34).Compared with low fish intake, moderate and high fish intake during pregnancy were associated with reduced levels of proinflammatory cytokines and adipokines in children. An integrated analysis identified a cluster of children with increased susceptibility to metabolic disease, which was (continued) Key Points Question Is fish consumption during pregnancy associated with benefits for the metabolic health of children? Findings In this cohort study of 805 mothers and their singleton offspring, ...

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“…While JAK/STAT signaling underlies diverse responses including mammary gland development, hematopoiesis, and immune cell development (Watson & Burdon 1996;Ward et al 2000;Ghoreschi et al 2009), the statistical enrichment of this PANTHER pathway is particularly intriguing due to its known function in organism growth (Yakar et al 2018) and metabolism (Dodington et al 2018). Knockout experiments in mouse models demonstrate the impacts of multiple JAKs and STATs on bone development and body mass (Jiliang Li 2013).…”

Section: Discussionmentioning

confidence: 99%

Genomic signatures of extreme body size divergence in baboons

Chiou

Bergey

Burrell

et al. 2019

Preprint

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Kinda and gray-footed chacma baboons occupy opposite extremes of the body size distribution in extant baboons (genus Papio). In order to detect signatures of natural selection in these two species, we genotyped 24,790 genome-wide autosomal SNPs from populations of Zambian baboons using double digest RADseq. We scanned the genome for evidence of selection by identifying regions with extreme differentiation between populations. We find evidence of selection on body size influencing multiple genes in one or both species, including FGF1, ATXN2, and PRKCE. We also find an enriched signal of selection associated with biological processes involved in multicellular organism growth and development, cell proliferation and cell growth, nutrient metabolism, and chondrocyte differentiation. Finally, we find that selection has impacted components of the CCKR signaling pathway, which regulates food intake and metabolism, and the JAK/STAT signaling pathway, which mediates the effect of cytokine signals on processes including epiphyseal chondrocyte proliferation essential for longitudinal bone growth. Our findings highlight promising avenues for future studies disentangling the genetic architecture of body size in primates including humans.

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JAK/STAT – Emerging Players in Metabolism

Cited by 214 publications

References 78 publications

Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

Induction of SOCS Expression by EV71 Infection Promotes EV71 Replication

Association of Fish Consumption and Mercury Exposure During Pregnancy With Metabolic Health and Inflammatory Biomarkers in Children

Genomic signatures of extreme body size divergence in baboons

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